On the nomenclatural status of type genera in Coleoptera (Insecta).

More than 4700 nominal family-group names (including names for fossils and ichnotaxa) are nomenclaturally available in the order Coleoptera. Since each family-group name is based on the concept of its type genus, we argue that the stability of names used for the classification of beetles depends on accurate nomenclatural data for each type genus. Following a review of taxonomic literature, with a focus on works that potentially contain type species designations, we provide a synthesis of nomenclatural data associated with the type genus of each nomenclaturally available family-group name in Coleoptera. For each type genus the author(s), year of publication, and page number are given as well as its current status (i.e., whether treated as valid or not) and current classification. Information about the type species of each type genus and the type species fixation (i.e., fixed originally or subsequently, and if subsequently, by whom) is also given. The original spelling of the family-group name that is based on each type genus is included, with its author(s), year, and stem. We append a list of nomenclaturally available family-group names presented in a classification scheme. Because of the importance of the Principle of Priority in zoological nomenclature, we provide information on the date of publication of the references cited in this work, when known. Several nomenclatural issues emerged during the course of this work. We therefore appeal to the community of coleopterists to submit applications to the International Commission on Zoological Nomenclature (henceforth "Commission") in order to permanently resolve some of the problems outlined here. The following changes of authorship for type genera are implemented here (these changes do not affect the concept of each type genus): CHRYSOMELIDAE: Fulcidax Crotch, 1870 (previously credited to "Clavareau, 1913"); CICINDELIDAE: Euprosopus W.S. MacLeay, 1825 (previously credited to "Dejean, 1825"); COCCINELLIDAE: Alesia Reiche, 1848 (previously credited to "Mulsant, 1850"); CURCULIONIDAE: Arachnopus Boisduval, 1835 (previously credited to "Guérin-Méneville, 1838"); ELATERIDAE: Thylacosternus Gemminger, 1869 (previously credited to "Bonvouloir, 1871"); EUCNEMIDAE: Arrhipis Gemminger, 1869 (previously credited to "Bonvouloir, 1871"), Mesogenus Gemminger, 1869 (previously credited to "Bonvouloir, 1871"); LUCANIDAE: Sinodendron Hellwig, 1791 (previously credited to "Hellwig, 1792"); PASSALIDAE: Neleides Harold, 1868 (previously credited to "Kaup, 1869"), Neleus Harold, 1868 (previously credited to "Kaup, 1869"), Pertinax Harold, 1868 (previously credited to "Kaup, 1869"), Petrejus Harold, 1868 (previously credited to "Kaup, 1869"), Undulifer Harold, 1868 (previously credited to "Kaup, 1869"), Vatinius Harold, 1868 (previously credited to "Kaup, 1869"); PTINIDAE: Mezium Leach, 1819 (previously credited to "Curtis, 1828"); PYROCHROIDAE: Agnathus Germar, 1818 (previously credited to "Germar, 1825"); SCARABAEIDAE: Eucranium Dejean, 1833 (previously "Brullé, 1838"). The following changes of type species were implemented following the discovery of older type species fixations (these changes do not pose a threat to nomenclatural stability): BOLBOCERATIDAE: Bolbocerusbocchus Erichson, 1841 for Bolbelasmus Boucomont, 1911 (previously Bolbocerasgallicum Mulsant, 1842); BUPRESTIDAE: Stigmoderaguerinii Hope, 1843 for Neocuris Saunders, 1868 (previously Anthaxiafortnumi Hope, 1846), Stigmoderaperoni Laporte & Gory, 1837 for Curis Laporte & Gory, 1837 (previously Buprestiscaloptera Boisduval, 1835); CARABIDAE: Carabuselatus Fabricius, 1801 for Molops Bonelli, 1810 (previously Carabusterricola Herbst, 1784 sensu Fabricius, 1792); CERAMBYCIDAE: Prionuspalmatus Fabricius, 1792 for Macrotoma Audinet-Serville, 1832 (previously Prionusserripes Fabricius, 1781); CHRYSOMELIDAE: Donaciaequiseti Fabricius, 1798 for Haemonia Dejean, 1821 (previously Donaciazosterae Fabricius, 1801), Eumolpusruber Latreille, 1807 for Euryope Dalman, 1824 (previously Cryptocephalusrubrifrons Fabricius, 1787), Galerucaaffinis Paykull, 1799 for Psylliodes Latreille, 1829 (previously Chrysomelachrysocephala Linnaeus, 1758); COCCINELLIDAE: Dermestesrufus Herbst, 1783 for Coccidula Kugelann, 1798 (previously Chrysomelascutellata Herbst, 1783); CRYPTOPHAGIDAE: Ipscaricis G.-A. Olivier, 1790 for Telmatophilus Heer, 1841 (previously Cryptophagustyphae Fallén, 1802), Silphaevanescens Marsham, 1802 for Atomaria Stephens, 1829 (previously Dermestesnigripennis Paykull, 1798); CURCULIONIDAE: Bostrichuscinereus Herbst, 1794 for Crypturgus Erichson, 1836 (previously Bostrichuspusillus Gyllenhal, 1813); DERMESTIDAE: Dermestestrifasciatus Fabricius, 1787 for Attagenus Latreille, 1802 (previously Dermestespellio Linnaeus, 1758); ELATERIDAE: Elatersulcatus Fabricius, 1777 for Chalcolepidius Eschscholtz, 1829 (previously Chalcolepidiuszonatus Eschscholtz, 1829); ENDOMYCHIDAE: Endomychusrufitarsis Chevrolat, 1835 for Epipocus Chevrolat, 1836 (previously Endomychustibialis Guérin-Méneville, 1834); EROTYLIDAE: Ipshumeralis Fabricius, 1787 for Dacne Latreille, 1797 (previously Dermestesbipustulatus Thunberg, 1781); EUCNEMIDAE: Fornaxaustrocaledonicus Perroud & Montrouzier, 1865 for Mesogenus Gemminger, 1869 (previously Mesogenusmellyi Bonvouloir, 1871); GLAPHYRIDAE: Melolonthaserratulae Fabricius, 1792 for Glaphyrus Latreille, 1802 (previously Scarabaeusmaurus Linnaeus, 1758); HISTERIDAE: Histerstriatus Forster, 1771 for Onthophilus Leach, 1817 (previously Histersulcatus Moll, 1784); LAMPYRIDAE: Ototretafornicata E. Olivier, 1900 for Ototreta E. Olivier, 1900 (previously Ototretaweyersi E. Olivier, 1900); LUCANIDAE: Lucanuscancroides Fabricius, 1787 for Lissotes Westwood, 1855 (previously Lissotesmenalcas Westwood, 1855); MELANDRYIDAE: Nothusclavipes G.-A. Olivier, 1812 for Nothus G.-A. Olivier, 1812 (previously Nothuspraeustus G.-A. Olivier, 1812); MELYRIDAE: Lagriaater Fabricius, 1787 for Enicopus Stephens, 1830 (previously Dermesteshirtus Linnaeus, 1767); NITIDULIDAE: Sphaeridiumluteum Fabricius, 1787 for Cychramus Kugelann, 1794 (previously Strongylusquadripunctatus Herbst, 1792); OEDEMERIDAE: Helopslaevis Fabricius, 1787 for Ditylus Fischer, 1817 (previously Ditylushelopioides Fischer, 1817 [sic]); PHALACRIDAE: Sphaeridiumaeneum Fabricius, 1792 for Olibrus Erichson, 1845 (previously Sphaeridiumbicolor Fabricius, 1792); RHIPICERIDAE: Sandalusniger Knoch, 1801 for Sandalus Knoch, 1801 (previously Sandaluspetrophya Knoch, 1801); SCARABAEIDAE: Cetoniaclathrata G.-A. Olivier, 1792 for Inca Lepeletier & Audinet-Serville, 1828 (previously Cetoniaynca Weber, 1801); Gnathoceravitticollis W. Kirby, 1825 for Gnathocera W. Kirby, 1825 (previously Gnathoceraimmaculata W. Kirby, 1825); Melolonthavillosula Illiger, 1803 for Chasmatopterus Dejean, 1821 (previously Melolonthahirtula Illiger, 1803); STAPHYLINIDAE: Staphylinuspolitus Linnaeus, 1758 for Philonthus Stephens, 1829 (previously Staphylinussplendens Fabricius, 1792); ZOPHERIDAE: Hispamutica Linnaeus, 1767 for Orthocerus Latreille, 1797 (previously Tenebriohirticornis DeGeer, 1775). The discovery of type species fixations that are older than those currently accepted pose a threat to nomenclatural stability (an application to the Commission is necessary to address each problem): CANTHARIDAE: Malthinus Latreille, 1805, Malthodes Kiesenwetter, 1852; CARABIDAE: Bradycellus Erichson, 1837, Chlaenius Bonelli, 1810, Harpalus Latreille, 1802, Lebia Latreille, 1802, Pheropsophus Solier, 1834, Trechus Clairville, 1806; CERAMBYCIDAE: Callichroma Latreille, 1816, Callidium Fabricius, 1775, Cerasphorus Audinet-Serville, 1834, Dorcadion Dalman, 1817, Leptura Linnaeus, 1758, Mesosa Latreille, 1829, Plectromerus Haldeman, 1847; CHRYSOMELIDAE: Amblycerus Thunberg, 1815, Chaetocnema Stephens, 1831, Chlamys Knoch, 1801, Monomacra Chevrolat, 1836, Phratora Chevrolat, 1836, Stylosomus Suffrian, 1847; COLONIDAE: Colon Herbst, 1797; CURCULIONIDAE: Cryphalus Erichson, 1836, Lepyrus Germar, 1817; ELATERIDAE: Adelocera Latreille, 1829, Beliophorus Eschscholtz, 1829; ENDOMYCHIDAE: Amphisternus Germar, 1843, Dapsa Latreille, 1829; GLAPHYRIDAE: Anthypna Eschscholtz, 1818; HISTERIDAE: Hololepta Paykull, 1811, Trypanaeus Eschscholtz, 1829; LEIODIDAE: Anisotoma Panzer, 1796, Camiarus Sharp, 1878, Choleva Latreille, 1797; LYCIDAE: Calopteron Laporte, 1838, Dictyoptera Latreille, 1829; MELOIDAE: Epicauta Dejean, 1834; NITIDULIDAE: Strongylus Herbst, 1792; SCARABAEIDAE: Anisoplia Schönherr, 1817, Anticheira Eschscholtz, 1818, Cyclocephala Dejean, 1821, Glycyphana Burmeister, 1842, Omaloplia Schönherr, 1817, Oniticellus Dejean, 1821, Parachilia Burmeister, 1842, Xylotrupes Hope, 1837; STAPHYLINIDAE: Batrisus Aubé, 1833, Phloeonomus Heer, 1840, Silpha Linnaeus, 1758; TENEBRIONIDAE: Bolitophagus Illiger, 1798, Mycetochara Guérin-Méneville, 1827. Type species are fixed for the following nominal genera: ANTHRIBIDAE: Decataphanesgracilis Labram & Imhoff, 1840 for Decataphanes Labram & Imhoff, 1840; CARABIDAE: Feroniaerratica Dejean, 1828 for Loxandrus J.L. LeConte, 1853; CERAMBYCIDAE: Tmesisternusoblongus Boisduval, 1835 for Icthyosoma Boisduval, 1835; CHRYSOMELIDAE: Brachydactylaannulipes Pic, 1913 for Pseudocrioceris Pic, 1916, Cassidaviridis Linnaeus, 1758 for Evaspistes Gistel, 1856, Ocnosceliscyanoptera Erichson, 1847 for Ocnoscelis Erichson, 1847, Promecothecapetelii Guérin-Méneville, 1840 for Promecotheca Guérin- Méneville, 1840; CLERIDAE: Attelabusmollis Linnaeus, 1758 for Dendroplanetes Gistel, 1856; CORYLOPHIDAE: Corylophusmarginicollis J.L. LeConte, 1852 for Corylophodes A. Matthews, 1885; CURCULIONIDAE: Hoplorhinusmelanocephalus Chevrolat, 1878 for Hoplorhinus Chevrolat, 1878; SonnetiusbinariusCasey, 1922 for Sonnetius Casey, 1922; ELATERIDAE: Pyrophorusmelanoxanthus Candèze, 1865 for Alampes Champion, 1896; PHYCOSECIDAE: Phycosecislitoralis Pascoe, 1875 for Phycosecis Pascoe, 1875; PTILODACTYLIDAE: Aploglossasallei Guérin-Méneville, 1849 for Aploglossa Guérin-Méneville, 1849, Coloboderaovata Klug, 1837 for Colobodera Klug, 1837; PTINIDAE: Dryophilusanobioides Chevrolat, 1832 for Dryobia Gistel, 1856; SCARABAEIDAE: Achloahelvola Erichson, 1840 for Achloa Erichson, 1840, Camentaobesa Burmeister, 1855 for Camenta Erichson, 1847, Pinotustalaus Erichson, 1847 for Pinotus Erichson, 1847, Psilonychusecklonii Burmeister, 1855 for Psilonychus Burmeister, 1855. New replacement name: CERAMBYCIDAE: Basorus Bouchard & Bousquet, nom. nov. for Sobarus Harold, 1879. New status: CARABIDAE: KRYZHANOVSKIANINI Deuve, 2020, stat. nov. is given the rank of tribe instead of subfamily since our classification uses the rank of subfamily for PAUSSINAE rather than family rank; CERAMBYCIDAE: Amymoma Pascoe, 1866, stat. nov. is used as valid over Neoamymoma Marinoni, 1977, Holopterus Blanchard, 1851, stat. nov. is used as valid over Proholopterus Monné, 2012; CURCULIONIDAE: Phytophilus Schönherr, 1835, stat. nov. is used as valid over the unnecessary new replacement name Synophthalmus Lacordaire, 1863; EUCNEMIDAE: Nematodinus Lea, 1919, stat. nov. is used as valid instead of Arrhipis Gemminger, 1869, which is a junior homonym. Details regarding additional nomenclatural issues that still need to be resolved are included in the entry for each of these type genera: BOSTRICHIDAE: Lyctus Fabricius, 1792; BRENTIDAE: Trachelizus Dejean, 1834; BUPRESTIDAE: Pristiptera Dejean, 1833; CANTHARIDAE: Chauliognathus Hentz, 1830, Telephorus Schäffer, 1766; CARABIDAE: Calathus Bonelli, 1810, Cosnania Dejean, 1821, Dicrochile Guérin-Méneville, 1847, Epactius D.H. Schneider, 1791, Merismoderus Westwood, 1847, Polyhirma Chaudoir, 1850, Solenogenys Westwood, 1860, Zabrus Clairville, 1806; CERAMBYCIDAE: Ancita J. Thomson, 1864, Compsocerus Audinet-Serville, 1834, Dorcadodium Gistel, 1856, Glenea Newman, 1842; Hesperophanes Dejean, 1835, Neoclytus J. Thomson, 1860, Phymasterna Laporte, 1840, Tetrops Stephens, 1829, Zygocera Erichson, 1842; CHRYSOMELIDAE: Acanthoscelides Schilsky, 1905, Corynodes Hope, 1841, Edusella Chapuis, 1874; Hemisphaerota Chevrolat, 1836; Physonota Boheman, 1854, Porphyraspis Hope, 1841; CLERIDAE: Dermestoides Schäffer, 1777; COCCINELLIDAE: Hippodamia Chevrolat, 1836, Myzia Mulsant, 1846, Platynaspis L. Redtenbacher, 1843; CURCULIONIDAE: Coeliodes Schönherr, 1837, Cryptoderma Ritsema, 1885, Deporaus Leach, 1819, Epistrophus Kirsch, 1869, Geonemus Schönherr, 1833, Hylastes Erichson, 1836; DYTISCIDAE: Deronectes Sharp, 1882, Platynectes Régimbart, 1879; EUCNEMIDAE: Dirhagus Latreille, 1834; HYBOSORIDAE: Ceratocanthus A. White, 1842; HYDROPHILIDAE: Cyclonotum Erichson, 1837; LAMPYRIDAE: Luciola Laporte, 1833; LEIODIDAE: Ptomaphagus Hellwig, 1795; LUCANIDAE: Leptinopterus Hope, 1838; LYCIDAE: Cladophorus Guérin-Méneville, 1830, Mimolibnetis Kazantsev, 2000; MELOIDAE: Mylabris Fabricius, 1775; NITIDULIDAE: Meligethes Stephens, 1829; PTILODACTYLIDAE: Daemon Laporte, 1838; SCARABAEIDAE: Allidiostoma Arrow, 1940, Heterochelus Burmeister, 1844, Liatongus Reitter, 1892, Lomaptera Gory & Percheron, 1833, Megaceras Hope, 1837, Stenotarsia Burmeister, 1842; STAPHYLINIDAE: Actocharis Fauvel, 1871, Aleochara Gravenhorst, 1802; STENOTRACHELIDAE: Stenotrachelus Berthold, 1827; TENEBRIONIDAE: Cryptochile Latreille, 1828, Heliopates Dejean, 1834, Helops Fabricius, 1775. First Reviser actions deciding the correct original spelling: CARABIDAE: Aristochroodes Marcilhac, 1993 (not Aritochroodes); CERAMBYCIDAE: Dorcadodium Gistel, 1856 (not Dorcadodion), EVODININI Zamoroka, 2022 (not EVODINIINI); CHRYSOMELIDAE: Caryopemon Jekel, 1855 (not Carpopemon), Decarthrocera Laboissière, 1937 (not Decarthrocerina); CICINDELIDAE: Odontocheila Laporte, 1834 (not Odontacheila); CLERIDAE: CORMODINA Bartlett, 2021 (not CORMODIINA), Orthopleura Spinola, 1845 (not Orthoplevra, not Orthopleuva); CURCULIONIDAE: Arachnobas Boisduval, 1835 (not Arachnopus), Palaeocryptorhynchus Poinar, 2009 (not Palaeocryptorhynus); DYTISCIDAE: Ambarticus Yang et al., 2019 and AMBARTICINI Yang et al., 2019 (not Ambraticus, not AMBRATICINI); LAMPYRIDAE: Megalophthalmus G.R. Gray, 1831 (not Megolophthalmus, not Megalopthalmus); SCARABAEIDAE: Mentophilus Laporte, 1840 (not Mintophilus, not Minthophilus), Pseudadoretusdilutellus Semenov, 1889 (not P.ditutellus). While the correct identification of the type species is assumed, in some cases evidence suggests that species were misidentified when they were fixed as the type of a particular nominal genus. Following the requirements of Article 70.3.2 of the International Code of Zoological Nomenclature we hereby fix the following type species (which in each case is the taxonomic species actually involved in the misidentification): ATTELABIDAE: Rhynchitescavifrons Gyllenhal, 1833 for Lasiorhynchites Jekel, 1860; BOSTRICHIDAE: Ligniperdaterebrans Pallas, 1772 for Apate Fabricius, 1775; BRENTIDAE: Ceocephalusappendiculatus Boheman, 1833 for Uroptera Berthold, 1827; BUPRESTIDAE: Buprestisundecimmaculata Herbst, 1784 for Ptosima Dejean, 1833; CARABIDAE: Amaralunicollis Schiødte, 1837 for Amara Bonelli, 1810, Buprestisconnexus Geoffroy, 1785 for Polistichus Bonelli, 1810, Carabusatrorufus Strøm, 1768 for Patrobus Dejean, 1821, Carabusgigas Creutzer, 1799 for Procerus Dejean, 1821, Carabusteutonus Schrank, 1781 for Stenolophus Dejean, 1821, Carenumbonellii Westwood, 1842 for Carenum Bonelli, 1813, Scaritespicipes G.-A. Olivier, 1795 for Acinopus Dejean, 1821, Trigonotomaindica Brullé, 1834 for Trigonotoma Dejean, 1828; CERAMBYCIDAE: Cerambyxlusitanus Linnaeus, 1767 for Exocentrus Dejean, 1835, Clytussupernotatus Say, 1824 for Psenocerus J.L. LeConte, 1852; CICINDELIDAE: Ctenostomajekelii Chevrolat, 1858 for Ctenostoma Klug, 1821; CURCULIONIDAE: Cnemogonuslecontei Dietz, 1896 for Cnemogonus J.L. LeConte, 1876; Phloeophagusturbatus Schönherr, 1845 for Phloeophagus Schönherr, 1838; GEOTRUPIDAE: Lucanusapterus Laxmann, 1770 for Lethrus Scopoli, 1777; HISTERIDAE: Histerrugiceps Duftschmid, 1805 for Hypocaccus C.G. Thomson, 1867; HYBOSORIDAE: Hybosorusilligeri Reiche, 1853 for Hybosorus W.S. MacLeay, 1819; HYDROPHILIDAE: Hydrophilusmelanocephalus G.-A. Olivier, 1793 for Enochrus C.G. Thomson, 1859; MYCETAEIDAE: Dermestessubterraneus Fabricius, 1801 for Mycetaea Stephens, 1829; SCARABAEIDAE: Aulaciumcarinatum Reiche, 1841 for Mentophilus Laporte, 1840, Phanaeusvindex W.S. MacLeay, 1819 for Phanaeus W.S. MacLeay, 1819, Ptinusgermanus Linnaeus, 1767 for Rhyssemus Mulsant, 1842, Scarabaeuslatipes Guérin-Méneville, 1838 for Cheiroplatys Hope, 1837; STAPHYLINIDAE: Scydmaenustarsatus P.W.J. Müller & Kunze, 1822 for Scydmaenus Latreille, 1802. New synonyms: CERAMBYCIDAE: CARILIINI Zamoroka, 2022, syn. nov. of ACMAEOPINI Della Beffa, 1915, DOLOCERINI Özdikmen, 2016, syn. nov. of BRACHYPTEROMINI Sama, 2008, PELOSSINI Tavakilian, 2013, syn. nov. of LYGRINI Sama, 2008, PROHOLOPTERINI Monné, 2012, syn. nov. of HOLOPTERINI Lacordaire, 1868.

Body reprogramming for fibromyalgia and central sensitivity syndrome: A preliminary evaluation.

Objectives: Central sensitivity syndrome disorders such as fibromyalgia, provoke continued debate, highlighting diagnostic and therapeutic uncertainty. The Hyland model provides a way of understanding and treating the medically unexplained symptoms of central sensitivity syndromes using complexity theory and principles of adaption in network systems. The body reprogramming is a multi-modal intervention based on the Hyland model designed for patients living with medically unexplained symptoms. This preliminary, naturalistic and single-arm service evaluation set out to evaluate outcome after attending a body reprogramming course in patients living with fibromyalgia or central sensitivity syndrome. Methods: Patients diagnosed with fibromyalgia or central sensitivity syndrome were recruited. The body reprogramming courses consisting of eight sessions, each 2.5 h in length, were run at two study sites in England. Data were collected at baseline, post course and 3-months post course using questionnaires assessing symptomatology (FIQR/SIQR), Depression (PHQ9), Anxiety (GAD7) and quality of life (GQoL). Repeated measures t-tests were used, and all comparisons were conducted on an intention to treat basis. Results: In total, 198 patients with a mean age of 47.73 years were enrolled on the body reprogramming courses. Statistically and clinically significant improvement were observed in the FIQR from baseline to post course (mean change: 11.28) and baseline to follow-up (mean change: 15.09). PHQ9 scores also improved significantly from baseline to post course (mean reduction 3.72) and baseline to follow-up (mean reduction 5.59). Conclusions: Our study provides first evidence that the body reprogramming intervention is an effective approach for patients living with fibromyalgia or central sensitivity syndromes on a variety of clinical measures. Besides these promising results, important limitations of the study are discussed, and larger randomized controlled trials are clearly warranted.

A tumour-spheroid manufacturing and cryopreservation process that yields a highly reproducible product ready for direct use in drug screening assays.

If it were possible to purchase tumour-spheroids as a standardised product, ready for direct use in assays, this may contribute to greater research reproducibility, potentially reducing costs and accelerating outcomes. Herein, we describe a workflow where uniformly sized cancer tumour-spheroids are mass-produced using microwell culture, cryopreserved with high viability, and then cultured in neutral buoyancy media for drug testing. C4-2B prostate cancer or MCF-7 breast cancer cells amalgamated into uniform tumour-spheroids after 48 h of culture. Tumour-spheroids formed from 100 cells each tolerated the cryopreservation process marginally better than tumour-spheroids formed from 200 or 400 cells. Post-thaw, tumour-spheroid metabolic activity was significantly reduced, suggesting mitochondrial damage. Metabolic function was rescued by thawing the tumour-spheroids into medium supplemented with 10 µM N-Acetyl-l-cysteine (NAC). Following thaw, the neutral buoyancy media, Happy Cell ASM, was used to maintain tumour-spheroids as discrete tissues during drug testing. Fresh and cryopreserved C4-2B or MCF-7 tumour-spheroids responded similarly to titrations of Docetaxel. This protocol will contribute to a future where tumour-spheroids may be available for purchase as reliable and reproducible products, allowing laboratories to efficiently replicate and build on published research, in many cases, making tumour-spheroids simply another cell culture reagent.

Aleocharine rove beetles of New Hampshire, USA: new taxa and new records (Coleoptera, Staphylinidae, Aleocharinae).

Based on the specimens housed primarily in the University of New Hampshire Insect Collection (UNH) and the Canadian National Collection (CNC), we present here a comprehensive faunal review of aleocharine beetles of the state and provide new distribution and natural history data. We report 252 species from New Hampshire belonging to some 74 genera in 15 tribes; 159 of these constitute new New Hampshire state records (NSR), of which 37 (excluding new species and including 1 New York record) constitute new country distribution records (NCR) for the USA. In addition, we provide 36 new state records for ME, with 5 of these species not yet known from NH, seven new state records for MA, two new state records for PA and VT, and one each for CT, DE, MI, NC, NY (also a NCR), OH, and OK. One new genus, Belladonna Klimaszewski and Chandler is erected, and nine species are described as new to science (alphabetical order): Agaricomorpha hampshirensis Klimaszewski and Chandler, sp. n., Atheta ellisi Klimaszewski and Chandler sp. n, Atheta monroe Klimaszewski and Chandler, sp. n., Atheta struyvei Klimaszewski and Chandler sp. n, Belladonna barryi Klimaszewski and Chandler, sp. n., Belladonna fortieri Klimaszewski and Chandler, sp. n., Colusa smetanai Klimaszewski and Chandler, sp. n., Philhygra pinkhami Klimaszewski and Chandler sp. n., and P. pseudomagniceps Klimaszewski and Chandler, sp. n. Undescribed females of Aleochara daviesi Klimaszewski and Brunke, and Silusa langori Klimaszewski, are described and illustrated. Illustrations of Atheta (Tetropla) tubericauda Bernhauer are provided for the first time, based on a male from New Hampshire. A new combination is proposed for Atheta (Dimetrota) mcalpinei Klimaszewski and Webster.

Review of genus-group names in the family Tenebrionidae (Insecta, Coleoptera).

A review of genus-group names for darkling beetles in the family Tenebrionidae (Insecta: Coleoptera) is presented. A catalogue of 4122 nomenclaturally available genus-group names, representing 2307 valid genera (33 of which are extinct) and 761 valid subgenera, is given. For each name the author, date, page number, gender, type species, type fixation, current status, and first synonymy (when the name is a synonym) are provided. Genus-group names in this family are also recorded in a classification framework, along with data on the distribution of valid genera and subgenera within major biogeographical realms. A list of 535 unavailable genus-group names (e.g., incorrect subsequent spellings) is included. Notes on the date of publication of references cited herein are given, when known. The following genera and subgenera are made available for the first time: Anemiadena Bouchard & Bousquet, subgen. nov. (in Cheirodes Gené, 1839), Armigena Bouchard & Bousquet, subgen. nov. (in Nesogena Mäklin, 1863), Debeauxiella Bouchard & Bousquet, subgen. nov. (in Hyperops Eschscholtz, 1831), Hyperopsis Bouchard & Bousquet, subgen. nov. (in Hyperops Eschscholtz, 1831), Linio Bouchard & Bousquet, subgen. nov. (in Nilio Latreille, 1802), Matthewsotys Bouchard & Bousquet, gen. nov., Neosolenopistoma Bouchard & Bousquet, subgen. nov. (in Eurynotus W. Kirby, 1819), Paragena Bouchard & Bousquet, subgen. nov. (in Nesogena Mäklin, 1863), Paulianaria Bouchard & Bousquet, gen. nov., Phyllechus Bouchard & Bousquet, gen. nov., Prorhytinota Bouchard & Bousquet, subgen. nov. (in Rhytinota Eschscholtz, 1831), Pseudorozonia Bouchard & Bousquet, subgen. nov. (in Rozonia Fairmaire, 1888), Pseudothinobatis Bouchard & Bousquet, gen. nov., Rhytinopsis Bouchard & Bousquet, subgen. nov. (in Thalpophilodes Strand, 1942), Rhytistena Bouchard & Bousquet, subgen. nov. (in Rhytinota Eschscholtz, 1831), Spinosdara Bouchard & Bousquet, subgen. nov. (in Osdara Walker, 1858), Spongesmia Bouchard & Bousquet, subgen. nov. (in Adesmia Fischer, 1822), and Zambesmia Bouchard & Bousquet, subgen. nov. (in Adesmia Fischer, 1822). The names Adeps Gistel, 1857 and Adepsion Strand, 1917 syn. nov. [= Tetraphyllus Laporte & Brullé, 1831], Asyrmatus Canzoneri, 1959 syn. nov. [= Pystelops Gozis, 1910], Euzadenos Koch, 1956 syn. nov. [= Selenepistoma Dejean, 1834], Gondwanodilamus Kaszab, 1969 syn. nov. [= Conibius J.L. LeConte, 1851], Gyrinodes Fauvel, 1897 syn. nov. [= Nesotes Allard, 1876], Helopondrus Reitter, 1922 syn. nov. [= Horistelops Gozis, 1910], Hybonotus Dejean, 1834 syn. nov. [= Damatris Laporte, 1840], Iphthimera Reitter, 1916 syn. nov. [= Metriopus Solier, 1835], Lagriomima Pic, 1950 syn. nov. [= Neogria Borchmann, 1911], Orphelops Gozis, 1910 syn. nov. [= Nalassus Mulsant, 1854], Phymatium Billberg, 1820 syn. nov. [= Cryptochile Latreille, 1828], Prosoblapsia Skopin & Kaszab, 1978 syn. nov. [= Genoblaps Bauer, 1921], and Pseudopimelia Gebler, 1859 syn. nov. [= Lasiostola Dejean, 1834] are established as new synonyms (valid names in square brackets). Anachayus Bouchard & Bousquet, nom. nov. is proposed as a replacement name for Chatanayus Ardoin, 1957, Genateropa Bouchard & Bousquet, nom. nov. as a replacement name for Apterogena Ardoin, 1962, Hemipristula Bouchard & Bousquet, nom. nov. as a replacement name for Hemipristis Kolbe, 1903, Kochotella Bouchard & Bousquet, nom. nov. as a replacement name for Millotella Koch, 1962, Medvedevoblaps Bouchard & Bousquet, nom. nov. as a replacement name for Protoblaps G.S. Medvedev, 1998, and Subpterocoma Bouchard & Bousquet, nom. nov. is proposed as a replacement name for Pseudopimelia Motschulsky, 1860. Neoeutrapela Bousquet & Bouchard, 2013 is downgraded to a subgenus (stat. nov.) of Impressosora Pic, 1952. Anchomma J.L. LeConte, 1858 is placed in Stenosini: Dichillina (previously in Pimeliinae: Anepsiini); Entypodera Gerstaecker, 1871, Impressosora Pic, 1952 and Xanthalia Fairmaire, 1894 are placed in Lagriinae: Lagriini: Statirina (previously in Lagriinae: Lagriini: Lagriina); Loxostethus Triplehorn, 1962 is placed in Diaperinae: Diaperini: Diaperina (previously in Diaperinae: Diaperini: Adelinina); Periphanodes Gebien, 1943 is placed in Stenochiinae: Cnodalonini (previously in Tenebrioninae: Helopini); Zadenos Laporte, 1840 is downgraded to a subgenus (stat. nov.) of the older name Selenepistoma Dejean, 1834. The type species [placed in square brackets] of the following available genus-group names are designated for the first time: Allostrongylium Kolbe, 1896 [Allostrongylium silvestre Kolbe, 1896], Auristira Borchmann, 1916 [Auristira octocostata Borchmann, 1916], Blapidocampsia Pic, 1919 [Campsia pallidipes Pic, 1918], Cerostena Solier, 1836 [Cerostena deplanata Solier, 1836], Coracostira Fairmaire, 1899 [Coracostira armipes Fairmaire, 1899], Dischidus Kolbe, 1886 [Helops sinuatus Fabricius, 1801], Eccoptostoma Gebien, 1913 [Taraxides ruficrus Fairmaire, 1894], Ellaemus Pascoe, 1866 [Emcephalus submaculatus Brême, 1842], Epeurycaulus Kolbe, 1902 [Epeurycaulus aldabricus Kolbe, 1902], Euschatia Solier, 1851 [Euschatia proxima Solier, 1851], Heliocaes Bedel, 1906 [Blaps emarginata Fabricius, 1792], Hemipristis Kolbe, 1903 [Hemipristis ukamia Kolbe, 1903], Iphthimera Reitter, 1916 [Stenocara ruficornis Solier, 1835], Isopedus Stein, 1877 [Helops tenebrioides Germar, 1813], Malacova Fairmaire, 1898 [Malacova bicolor Fairmaire, 1898], Modicodisema Pic, 1917 [Disema subopaca Pic, 1912], Peltadesmia Kuntzen, 1916 [Metriopus platynotus Gerstaecker, 1854], Phymatium Billberg, 1820 [Pimelia maculata Fabricius, 1781], Podoces Péringuey, 1886 [Podoces granosula Péringuey, 1886], Pseuduroplatopsis Pic, 1913 [Borchmannia javana Pic, 1913], Pteraulus Solier, 1848 [Pteraulus sulcatipennis Solier, 1848], Sciaca Solier, 1835 [Hylithus disctinctus Solier, 1835], Sterces Champion, 1891 [Sterces violaceipennis Champion, 1891] and Teremenes Carter, 1914 [Tenebrio longipennis Hope, 1843]. Evidence suggests that some type species were misidentified. In these instances, information on the misidentification is provided and, in the following cases, the taxonomic species actually involved is fixed as the type species [placed in square brackets] following requirements in Article 70.3 of the International Code of Zoological Nomenclature: Accanthopus Dejean, 1821 [Tenebrio velikensis Piller & Mitterpacher, 1783], Becvaramarygmus Masumoto, 1999 [Dietysus nodicornis Gravely, 1915], Heterophaga Dejean, 1834 [Opatrum laevigatum Fabricius, 1781], Laena Dejean, 1821, [Scaurus viennensis Sturm, 1807], Margus Dejean, 1834 [Colydium castaneum Herbst, 1797], Pachycera Eschscholtz, 1831 [Tenebrio buprestoides Fabricius, 1781], Saragus Erichson, 1842 [Celibe costata Solier, 1848], Stene Stephens, 1829 [Colydium castaneum Herbst, 1797], Stenosis Herbst, 1799 [Tagenia intermedia Solier, 1838] and Tentyriopsis Gebien, 1928 [Tentyriopsis pertyi Gebien, 1940]. The following First Reviser actions are proposed to fix the precedence of names or nomenclatural acts (rejected name or act in square brackets): Stenosis ciliaris Gebien, 1920 as the type species for Afronosis G.S. Medvedev, 1995 [Stenosis leontjevi G.S. Medvedev, 1995], Alienoplonyx Bremer, 2019 [Alienolonyx], Amblypteraca Mas-Peinado, Buckley, Ruiz & García-París, 2018 [Amplypteraca], Caenocrypticoides Kaszab, 1969 [Caenocripticoides], Deriles Motschulsky, 1872 [Derilis], Eccoptostira Borchmann, 1936 [Ecoptostira], †Eodromus Haupt, 1950 [†Edromus], Eutelus Solier, 1843 [Lutelus], Euthriptera Reitter, 1893 [Enthriptera], Meglyphus Motschulsky, 1872 [Megliphus], Microtelopsis Koch, 1940 [Extetranosis Koch, 1940, Hypermicrotelopsis Koch, 1940], Neandrosus Pic, 1921 [Neoandrosus], Nodosogylium Pic, 1951 [Nodosogilium], Notiolesthus Motschulsky, 1872 [Notiolosthus], Pseudeucyrtus Pic, 1916 [Pseudocyrtus], Pseudotrichoplatyscelis Kaszab, 1960 [Pseudotrichoplatynoscelis and Pseudotrichoplatycelis], Rhydimorpha Koch, 1943 [Rhytimorpha], Rhophobas Motschulsky, 1872 [Rophobas], Rhyssochiton Gray, 1831 [Ryssocheton and Ryssochiton], Sphaerotidius Kaszab, 1941 [Spaerotidius], Stira Agassiz, 1846 (Mollusca) [Stira Agassiz, 1846 (Coleoptera)], Sulpiusoma Ferrer, 2006 [Sulpiosoma] and Taenobates Motschulsky, 1872 [Taeniobates]. Supporting evidence is provided for the conservation of usage of Cyphaleus Westwood, 1841 nomen protectum over Chrysobalus Boisduval, 1835 nomen oblitum.

Do patients with central sensitivity syndromes have poor subjective outcomes despite anatomical cure from pelvic organ prolapse surgery?

INTRODUCTION: Pelvic organ prolapse(POP) has an adverse impact on quality of life with lifetime risk of surgery varying from 11 to 20%. Conditions such as fibromyalgia (FMS), chronic fatigue syndrome (CFS/ME) and irritable bowel syndrome (IBS), collectively known as central sensitivity syndromes (CSS), may affect the outcome of POP surgery. The aim of this article is to compare the outcomes of vaginal POP surgery between women with and without CSS. METHOD: This was a prospective cohort study. The validated Central Sensitisation Inventory (CSI) was used to identify women with CSS. Subjective and objective outcomes were compared between the two groups using POP-SS, Expectation and satisfaction/"EGGS", pain scores and the POP quantification system (POP-Q). A non-parametric test was used for analysis. RESULT: Seventy-eight women were recruited. Complete data were available in 62 patients; 23 patients had evidence of CSS and 39 did not. Women with CSS had significantly higher pre- and post-operative POP-SS scores than those without (p < 0.0005, p = 0.004). Seventeen (73.9%) women with CSS compared to 38 (97.4%) women without CSS demonstrated improvement of a minimum 6 points on the POP-SS scale; however, this was not stastically significant. McGill's pain scores were higher in women with CSS both pre- and post-surgery. Ninety-five per cent of women without CSS achieved their goals and were satisfied with the surgery compared to 69.5% of women with CSS (p < 005). CONCLUSION: There is a less favourable outcome of POP surgery in women with CSS compared to those without in terms of persistence of symptoms, pain and overall satisfaction.

Effects of HER Family-targeting Tyrosine Kinase Inhibitors on Antibody-dependent Cell-mediated Cytotoxicity in HER2-expressing Breast Cancer.

PURPOSE: Antibody-dependent cell-mediated cytotoxicity (ADCC) is one mechanism of action of the monoclonal antibody (mAb) therapies trastuzumab and pertuzumab. Tyrosine kinase inhibitors (TKIs), like lapatinib, may have added therapeutic value in combination with mAbs through enhanced ADCC activity. Using clinical data, we examined the impact of lapatinib on HER2/EGFR expression levels and natural killer (NK) cell gene signatures. We investigated the ability of three TKIs (lapatinib, afatinib, and neratinib) to alter HER2/immune-related protein levels in preclinical models of HER2-positive (HER2+) and HER2-low breast cancer, and the subsequent effects on trastuzumab/pertuzumab-mediated ADCC. EXPERIMENTAL DESIGN: Preclinical studies (proliferation assays, Western blotting, high content analysis, and flow cytometry) employed HER2+ (SKBR3 and HCC1954) and HER2-low (MCF-7, T47D, CAMA-1, and CAL-51) breast cancer cell lines. NCT00524303 provided reverse phase protein array-determined protein levels of HER2/pHER2/EGFR/pEGFR. RNA-based NK cell gene signatures (CIBERSORT/MCP-counter) post-neoadjuvant anti-HER2 therapy were assessed (NCT00769470/NCT01485926). ADCC assays utilized flow cytometry-based protocols. RESULTS: Lapatinib significantly increased membrane HER2 levels, while afatinib and neratinib significantly decreased levels in all preclinical models. Single-agent lapatinib increased HER2 or EGFR levels in 10 of 11 (91%) tumor samples. NK cell signatures increased posttherapy (P = 0.03) and associated with trastuzumab response (P = 0.01). TKI treatment altered mAb-induced NK cell-mediated ADCC in vitro, but it did not consistently correlate with HER2 expression in HER2+ or HER2-low models. The ADCC response to trastuzumab and pertuzumab combined did not exceed either mAb alone. CONCLUSIONS: TKIs differentially alter tumor cell phenotype which can impact NK cell-mediated response to coadministered antibody therapies. mAb-induced ADCC response is relevant when rationalizing combinations for clinical investigation.

Correction to: Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer.

Since the publication of this work [1] and in response to a recent query that was brought to our attention in relation to the Western Blot in Figure 1(C) for NP2, protein lysates prepared around the same time as those presented in the manuscript in question, were run by SDS-PAGE under similar experimental conditions and probed using the same primary antibodies to NP1 and NP2 that were used originally.

Body Reprogramming: Reframing the Fibromyalgia narrative and providing an integrative therapeutic model.

We propose a theory known as the Hyland model to help conceptualise Fibromyalgia within a complex adaptive control system. A fundamental assumption is that symptom generating mechanisms are causally connected, forming a network that has emergent properties. An illness narrative has been developed which has a 'goodness of fit' with the lived experience of those with Fibromyalgia. The theory guides management within the clinical setting and incorporates current evidence-based therapeutic strategies, within a multi-modal intervention described as 'Body Reprogramming'. This intervention focuses on non-pharmacological and lifestyle-based considerations. The theoretical framework also helps explain why modest therapeutic effects are gained from current pharmacological options.

Targeting NF-κB-mediated inflammatory pathways in cisplatin-resistant NSCLC.

OBJECTIVES: The majority of patients with non-small cell lung cancer (NSCLC) present with advanced stage disease, at which time chemotherapy is usually the most common treatment option. While somewhat effective, patients treated with platinum-based regimens will eventually develop resistance, with others presenting with intrinsic resistance. Multiple pathways have been implicated in chemo-resistance, however the critical underlying mechanisms have yet to be elucidated. The aim of this project was to determine the role of inflammatory mediators in cisplatin-resistance in NSCLC. MATERIALS AND METHODS: Inflammatory mediator, NF-κB, and its associated pathways were investigated in an isogenic model of cisplatin-resistant NSCLC using age-matched parental (PT) and corresponding cisplatin-resistant (CisR) sublines. Pathways were assessed using mass spectrometry, western blot analysis and qRT-PCR. The cisplatin sensitizing potential of an NF-κB small molecule inhibitor, DHMEQ, was also assessed by means of viability assays and western blot analysis. RESULTS: Proteomic analysis identified dysregulated NF-κB responsive targets in CisR cells when compared to PT cells, with increased NF-κB expression identified in four out of the five NSCLC sub-types examined (CisR versus PT). DHMEQ treatment resulted in reduced NF-κB expression in the presence of cisplatin, and re-sensitized CisR cells to the cytotoxic effects of the drug. CONCLUSION: This study identified NF-ĸB as a potential therapeutic target in cisplatin-resistant NSCLC. Furthermore, inhibition of NF-ĸB using DHMEQ re-sensitized chemo-resistant cells to cisplatin treatment.

Symptom frequency and development of a generic functional disorder symptom scale suitable for use in studies of patients with irritable bowel syndrome, fibromyalgia syndrome or chronic fatigue syndrome.

OBJECTIVES: To describe the extent to which irritable bowel syndrome (IBS), fibromyalgia syndrome (FMS), and chronic fatigue syndrome (CFS) exhibit symptom overlap, and to validate a patient-derived, generic symptom questionnaire. METHODS: A patient-derived 61-item symptom-frequency questionnaire was completed by participants recruited through IBS, FMS and CFS self-help websites. Principal axis factor analysis with oblimin rotation was performed separately for those reporting an IBS, FMS or CFS diagnosis. RESULTS: Questionnaires were completed by 1751 participants of whom 851 reported more than one of the three diagnoses. Stomach pain on at least a weekly basis was reported by 79% of IBS, 52% of FMS, and 43% of CFS single diagnosis participants. Pain increasing the day after activity was reported by 32% of IBS, 94% of FMS, and 85% of CFS single diagnosis participants. Waking still tired at least once weekly was reported by 75% of IBS, 97% of FMS, and 95% of CFS single diagnosis participants. Exploratory factor analysis produced consistent results across all three diagnostic groups, the 61 items loading on 12 correlated factors with a single higher order factor on which all items loaded. Frequency analysis led to the rejection of one item (cold sores on or near lips), and freeform reporting by participants of additional symptoms identified an additional five, namely, restless legs, hair loss/brittle hair/thinning, dizziness/balance problems, blurred vision and urination problems. CONCLUSIONS: IBS, FMS and CFS are polysymptomatic spectrum disorders with a wide range of overlapping symptoms, many of which are unrelated to diagnostic criteria. Frequency analysis and factor analysis confirm the validity of using the same questionnaire across different diagnostic categories. The 65-item general symptom questionnaire (GSQ-65) is a valid generic symptom scale suitable for assessing the many different symptoms of people with IBS, FMS and CFS.

Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy?

Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability. Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy; however, many infants still experience lifelong disabilities to movement, sensation and cognition. Clinical guidelines, based on strong clinical and preclinical evidence, recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours, with a target brain temperature of 33.5 ± 0.5°C for infants with moderate to severe hypoxic-ischemic encephalopathy. The clinical guidelines also recommend that infants be rewarmed at a rate of 0.5°C per hour, but this is not based on strong evidence. There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy. Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia. In this review, we evaluate the evidence for the optimal start time, duration and depth of hypothermia, and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.

Fibronectin-conjugated thermoresponsive nanobridges generate three dimensional human pluripotent stem cell cultures for differentiation towards the neural lineages.

Production of 3-dimensional neural progenitor cultures from human pluripotent stem cells offers the potential to generate large numbers of cells. We utilised our nanobridge system to generate 3D hPSC aggregates for differentiation towards the neural lineage, and investigate the ability to passage aggregates while maintaining cells at a stem/progenitor stage. Over 38 days, aggregate cultures exhibited upregulation and maintenance of neural-associated markers and demonstrated up to 10 fold increase in cell number. Aggregates undergoing neural induction in the presence or absence of nanobridges demonstrated no differences in marker expression, proliferation or viability. However, aggregates formed without nanobridges were statistically significantly fewer and smaller by passage 3. Organoids, cultured from aggregates, and treated with retinoic acid or rock inhibitor demonstrated terminal differentiation as assessed by immunohistochemistry. These data demonstrate that nanobridge 3D hPSC can differentiate to neural stem/progenitor cells, and be maintained at this stage through serial passaging and expansion.

Media composition modulates human embryonic stem cell morphology and may influence preferential lineage differentiation potential.

Undifferentiated human embryonic stem cells have a distinct morphology (hESC). Changes in cell morphology during culture can be indicative of differentiation. hESC, maintained in diverse medias, demonstrated alterations in morphological parameters and subsequent alterations in underlying transcript expression and lineage differentiation. Analysis of morphological parameters showed distinct and significant differences between the undefined, less defined and Xeno-free medias while still maintaining pluripotency markers. This suggested that the less defined media may be creating dynamic instability in the cytoskeleton, with the cytoskeleton becoming more stabilised in the Xeno-free media as demonstrated by smaller and rounder cells. Examination of early lineage markers during undirected differentiation using d5 embryoid bodies demonstrated increased mesodermal lineage preference as compared to endodermal or ectoderm in cells originally cultured in Xeno-free media. Undefined media showed preference for mesoderm and ectoderm lineages, while less defined media (BSA present) demonstrated no preference. These data reveal that culture media may produce fundamental changes in cell morphology which are reflected in early lineage differentiation choice.

The proportion of women with central sensitivity syndrome in gynecology outpatient clinics (GOPDs).

INTRODUCTION AND HYPOTHESIS: Patients in gynecology outpatient clinics (GOPDs) may present with symptoms that do not correlate well with the observed pathology and are usually labelled as having a functional disorder or medically unexplained symptoms (MUS). Underlying central sensitivity syndrome (CSS) with central sensitization (CS) as a potential mechanism may be responsible for some of their symptoms. The aim of this study is to identify the proportion of women with central sensitivity syndrome attending GOPDs. METHODS: This was a prospective study. All women attending a GOPD included in the study were asked to complete a validated Central Sensitization Inventory (CSI). The responses were graded on a Likert scale from 0 (never) to 4 (always). The total score ranges from 0 to 100. For screening purposes, a single CSI cutoff score of 40 was used to identify the group of women who may have central sensitization syndrome. RESULTS: Three hundred twenty-six women participated in the study. Overall, 123 (37%) women achieved a score above 40. This could be interpreted as these patients having increased risk of underlying central sensitization. Of these, 43 had a previously confirmed diagnosis of migraine, 55 (44%) depression, 39 (31.7%) anxiety, 11 fibromyalgia (FM), 34 irritable bowel syndrome (IBS) and 16 chronic fatigue syndrome (CFS/ME). CONCLUSIONS: Managing patients and their expectations in gynecological outpatient departments when symptoms are inconsistent with observable pathological findings is challenging. This is further complicated when patients have a concomitant central sensitivity syndrome, which can also influence the surgical outcome. Identifying these patients is a key factor for appropriate management.

Low-radiation and high image quality coronary computed tomography angiography in "real-world" unselected patients.

AIM: To determine the radiation dose and image quality in coronary computed tomography angiography (CCTA) using state-of-the-art dose reduction methods in unselected "real world" patients. METHODS: In this single-centre study, consecutive patients in sinus rhythm underwent CCTA for suspected coronary artery disease (CAD) using a 320-row detector CT scanner. All patients underwent the standard CT acquisition protocol at our institute (Morriston Hospital) a combination of dose saving advances including prospective electrocardiogram-gating, automated tube current modulation, tube voltage reduction, heart rate reduction, and the most recent novel adaptive iterative dose reconstruction 3D (AIDR3D) algorithm. The cohort comprised real-world patients for routine CCTA who were not selected on age, body mass index, or heart rate. Subjective image quality was graded on a 4-point scale (4 = excellent, 1 = non-diagnostic). RESULTS: A total of 543 patients were included in the study with a mean body weight of 81 ± 18 kg and a pre-scan mean heart rate of 70 ± 11 beats per minute (bpm). When indicated, patients received rate-limiting medication with an oral beta-blocker followed by additional intravenous beta-blocker to achieve a heart rate below 65 bpm. The median effective radiation dose was 0.88 mSv (IQR, 0.6-1.4 mSv) derived from a Dose Length Product of 61.45 mGy.cm (IQR, 42.86-100.00 mGy.cm). This also includes what we believe to be the lowest ever-reported radiation dose for a routine clinical CCTA (0.18 mSv). The mean image quality (± SD) was 3.65 ± 0.61, with a subjective image quality score of 3 ("good") or above for 93% of patient CCTAs. CONCLUSION: Combining a low-dose scan protocol and AIDR3D with a 320-detector row CT scanner can provide high quality images at exceptionally low radiation dose in unselected patients being investigated for CAD.

Predicting Technical Success after Fistuloplasty: An Analysis of 176 Procedures.

BACKGROUND: Significant stenoses in arteriovenous fistulae (AVFs) or arteriovenous grafts (AVGs) with limitation of flow and dialysis inadequacy should prompt consideration for fistuloplasty. We sought to identify fistulae, lesions, and patient-specific variables, which predict for outcomes after fistuloplasty. METHODS: Data were extracted retrospectively from a renal access database from 2011 to 2016 of patients undergoing fistuloplasty. Demographics, comorbidities, outcomes of intervention, and flow rates documented on preintervention and postintervention duplex were collected. Secondary analysis of factors associated with postfistuloplasty flow rates of >600 mL/min, previously shown to be predictive of not requiring future intervention, was performed. RESULTS: Of 204 attempted fistuloplasties, 176 were completed. One hundred forty (79.5%) were native AVFs and 34 (19.3%), AVGs (no data for 2). Median stenosis treated was 75%, with a majority (43.8%) in the proximal outflow vein. Flow rate on duplex after fistuloplasty was significantly better in AVFs (mean improvement 189.2 mL/min) than that in AVGs (mean improvement 51.8 mL/min; P = 0.034). Greatest flow improvement occurred for needling site stenotic lesions compared with other locations (from anastomosis to central vein) but was not significant. Brachio-brachial or brachio-axillary AVGs did significantly (P < 0.05) worse than all other fistulae types. The presence of hypertension was predicted for postfistuloplasty flow rate of >600 mL/min. CONCLUSIONS: Flow rates after fistuloplasty vary depending on the type of fistula treated and the presence of hypertension. Knowledge of this can lead to better patient selection and counseling for fistuloplasty.

Tyrosine kinase inhibitors as modulators of trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity in breast cancer cell lines.

BACKGROUND: Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcÆ´R+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab. Using LDH-release assays, we investigated the impact of antigen modulation, assay duration and peripheral blood mononuclear cell (PBMC) activity on trastuzumab-mediated ADCC in breast cancer models of maximal (SKBR3) and minimal (MCF-7) target antigen expression to determine if modulating the ADCC response to trastuzumab using TKIs may be a viable approach for enhancing tumor immune reactivity. METHODS: HER2 levels were determined in lapatinib, afatinib and neratinib-treated SKBR3 and MCF-7 using high content analysis (HCA). Trastuzumab-mediated ADCC was assessed following treatment with TKIs utilising a colorimetric LDH release-based protocol at 4 and 12h timepoints. PBMC activity was assessed against non-MHC-restricted K562 cells. A flow cytometry-based method (CFSE/7-AAD) was also used to measure trastuzumab-mediated ADCC in medium-treated SKBR3 and MCF-7. RESULTS: HER2 antigen levels were significantly altered by the three TKIs in both cell line models. The TKIs significantly reduced LDH levels directly in SKBR3 cells but not MCF-7. Lapatinib and neratinib augment trastuzumab-related ADCC in SKBR3 but the effect was not consistent with antigen expression levels and was dependent on volunteer PBMC activity (vs. K562). A 12h assay timepoint produced more consistent results. Trastuzumab-mediated ADCC (PBMC:target cell ratio of 10:1) was measured at 7.6±4.7% (T12) by LDH assay and 19±3.2 % (T12) using the flow cytometry-based method in the antigen-low model MCF-7. CONCLUSIONS: In the presence of effector cells with high cytotoxic capacity, TKIs have the ability to augment the passive immunotherapeutic potential of trastuzumab in SKBR3, a model of HER2+ breast cancer. ADCC levels detected by LDH release assays are extremely low in MCF-7; the flow cytometry-based CFSE/7-AAD method is more sensitive and consistent for the determination of ADCC in HER2-low models.